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Reconstruction of the neurovascular unit is essential for the repair of spinal cord injury (SCI). Nonetheless, detailed documentation of specific vascular changes following SCI and targeted interventions for vascular treatment remains limited. This study demonstrates that traumatic pathological vascular remodeling occurs during the chronic phase of injury, characterized by enlarged vessel diameter, disruption of blood-spinal cord barrier, endothelial-to-mesenchymal transition (EndoMT), and heightened extracellular matrix deposition. After SCI, osteopontin (OPN), a critical factor secreted by immune cells, is indispensable for early vascular regeneration but also contributes to traumatic pathological vascular remodeling. This work further elucidates the mechanism by which OPN influences spinal cord microvascular endothelial cells, involving Akt-mediated Foxo1 phosphorylation. This process facilitates the extranuclear transport of Foxo1 and decreases Smad7 expression, leading to excessive activation of the TGF-β signaling pathway, which ultimately results in EndoMT and fibrosis. Targeted inhibition of Foxo1 phosphorylation through an endothelium-specific aptamer-liposome small molecule delivery system significantly mitigates vascular remodeling, thereby enhancing axon regeneration and neurological function recovery following SCI. The findings offer a novel perspective for drug therapies aimed at specifically targeting pathological vasculature after SCI., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Rationale: Spinal cord injury (SCI)-induced vascular damage causes ischemia and hypoxia at the injury site, which, in turn, leads to profound metabolic disruptions. The effects of these metabolic alterations on neural tissue remodeling and functional recovery have yet to be elucidated. The current study aimed to investigate the consequences of the SCI-induced hypoxic environment at the epicenter of the injury. Methods: This study employed metabolomics to assess changes in energy metabolism after SCI. The use of a lactate sensor identified lactate shuttle between endothelial cells (ECs) and neurons. Reanalysis of single-cell RNA sequencing data demonstrated reduced MCT1 expression in ECs after SCI. Additionally, an adeno-associated virus (AAV) overexpressing MCT1 was utilized to elucidate its role in endothelial-neuronal interactions, tissue repair, and functional recovery. Results: The findings revealed markedly decreased monocarboxylate transporter 1 (MCT1) expression that facilitates lactate delivery to neurons to support their energy metabolism in ECs post-SCI. This decreased expression of MCT1 disrupts lactate transport to neurons, resulting in a metabolic imbalance that impedes axonal regeneration. Strikingly, our results suggested that administering adeno-associated virus specifically to ECs to restore MCT1 expression enhances axonal regeneration and improves functional recovery in SCI mice. These findings indicate a novel link between lactate shuttling from endothelial cells to neurons following SCI and subsequent neural functional recovery. Conclusion: In summary, the current study highlights a novel metabolic pathway for therapeutic interventions in the treatment of SCI. Additionally, our findings indicate the potential benefits of targeting lactate transport mechanisms in recovery from SCI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Spinal infection caused by Parvimonas micra ( P. micra ) is a rare infection. The characteristic imageology includes spondylodiscitis, spondylitis, paravertebral abscess, and epidural abscess. One case of spondylodiscitis of lumbar complicated with spinal epidural abscess caused by P. micra was admitted to the Department of Spinal Surgery, Xiangya Hospital, Central South University on February, 2023. This case is a 60 years old man with lower back pain and left lower limb numbness. MRI showed spondylitis, spondylodiscitis, and epidural abscess. The patient underwent debridement, decompression and fusion surgery. The culture of surgical sample was negative. P. micra was detected by metagenomic next-generation sequencing (mNGS). The postoperative antibiotic treatment included intravenous infusion of linezolid and piperacillin for 1 week, then intravenous infusion of ceftazidime and oral metronidazole for 2 weeks, followed by oral metronidazole and nerofloxacin for 2 weeks. During the follow-up, the lower back pain and left lower limb numbness was complete remission. Spinal infection caused by P. micra is extremely rare, when the culture is negative, mNGS can help the final diagnosis.

Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), potentially exacerbating nerve damage and emphasizing the criticality of preserving the BSCB integrity during SCI treatment. This study explores an alternative therapeutic approach for SCI by identifying a subpopulation of exosomes with stable BSCB function and achieving a specific targeted delivery. Specific subpopulations of CD146 + CD271 + umbilical cord mesenchymal stem cells (UCMSCs) were isolated, from which engineered exosomes (RGD-CD146 + CD271 + UCMSC-Exos) with targeted neovascularization function were obtained through gene transfection. In vivo and in vitro experiments were performed to explore the targeting and therapeutic effects of RGD-CD146 + CD271 + UCMSC-Exos and the potential mechanisms underlying BSCB stabilization and neural function recovery. The results demonstrated that RGD-CD146 + CD271 + UCMSC-Exos exhibited physical and chemical properties similar to those of regular exosomes. Notably, following intranasal administration, RGD-CD146 + CD271 + UCMSC-Exos exhibited enhanced aggregation at the SCI center and demonstrated the specific targeting of neovascular endothelial cells. In the SCI model, intranasal administration of RGD-CD146 + CD271 + UCMSC-Exos reduced Evans blue dye leakage, increased tight junction protein expression, and improved neurological function recovery. In vitro testing revealed that RGD-CD146 + CD271 + UCMSC-Exos treatment significantly reduced the permeability of bEnd.3 cells subjected to oxygen-glucose deprivation, thereby restoring the integrity of tight junctions. Moreover, further exploration of the molecular mechanism underlying BSCB stabilization by CD146 + CD271 + UCMSC-Exos identified the crucial role of the miR-501-5p/MLCK axis in this process. In conclusion, targeted delivery of RGD-CD146 + CD271 + UCMSC-Exos presents a promising and effective treatment option for SCI.